Mice hypomorphic for Pitx3 define a minimal dopamine neuron population sufficient for entraining behavior and metabolism to scheduled feeding

SummaryPitx3ak mice lack a functioning retina and nearly all dopamine neurons of the substantia nigra (SN). del Rio-Marten et al (2019) reported that entrainment of circadian rhythms to daily light-dark and feeding schedules is absent in these mice. With food limited to 12h/day, food anticipatory circadian rhythms failed to emerge, and metabolic rhythms failed to synchronize with locomotor and feeding rhythms. The authors propose that retinal innervation of the suprachiasmatic nucleus clock is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms in Pitx3ak mice do not entrain to LD cycles, but we find no desynchrony between these rhythms nor a deficit in entrainment to daily feeding schedules. SN dopamine neurons surviving in Pitx3ak mice may define a mininum population sufficient for food entrainment.

The projections of ipRGCs and conventional RGCs to retinorecipient brain nuclei

ABSTRACTRetinal ganglion cells (RGCs), the output neurons of the retina, allow us to perceive our visual environment. RGCs respond to rod/cone input through the retinal circuitry, however, a small population of RGCs are in addition intrinsically photosensitive (ipRGCs) and project to unique targets in the brain to modulate a broad range of subconscious visual behaviors such as pupil constriction and circadian photoentrainment. Despite the discovery of ipRGCs nearly two decades ago, there is still little information about how or if conventional RGCs (non-ipRGCs) target ipRGC-recipient nuclei to influence subconscious visual behavior. Using a dual recombinase color strategy, we showed that conventional RGCs innervate many subconscious ipRGC-recipient nuclei, apart from the suprachiasmatic nucleus. We revealed previously unrecognized stratification patterns of retinal innervation from ipRGCs and conventional RGCs in the ventral portion of the lateral geniculate nucleus. Further, we found that the percent innervation of ipRGCs and conventional RGCs across ipsi- and contralateral nuclei differ. Our data provide a blueprint to understand how conventional RGCs and ipRGCs innervate different brain regions to influence subconscious visual behaviors.

Neuropeptide Y and enkephalin immunoreactivity in retinorecipient nuclei of the hamster pretectum and thalamus

This investigation was stimulated by the historical confusion concerning the identity of certain pretectal nuclei and by large differences reported between species with respect to which nuclei receive retinal innervation. Subcortical visual nuclei were studied using immunohistochemistry to identify retinal projections labeled following intraocular injection of cholera toxin, b fragment. In addition, neuropeptide Y (NPY) or enkephalin (ENK) immunoreactive cells and fibers were also evaluated in the retinorecipient pretectal and thalamic areas. The results confirm the established view that the retina directly innervates the nucleus of the optic tract (NOT), posterior (PPT) and olivary pretectal (OPT) nuclei. However, the retina also innervates the hamster medial (MPT) and anterior (APT; dorsal division) pretectal nuclei, results not previously reported in rodents. A commissural pretectal area (CPT) sparsely innervated by retina is also described. The data show for the first time that the posterior limitans nucleus (PLi) receives a moderately dense, direct retinal input. The PLi does not project to the cortex and appears to be a pretectal, rather than thalamic, nucleus. All retinal projections are bilateral, although predominantly contralateral The PLi contains a moderately dense plexus of NPY- and ENK-IR fibers and terminals. However, peptidergic fibes also traverse the APT and connect with the dorsomedial pretectum. The OPT contains ENK- and NPY-IR neurons and fibers, but is specifically identifiable by a moderately dense plexus of ENK-IR terminals. Numerous ENK-IR neurons are found in the NOT and PPT. The latter also has moderate numbers of ENK-IR fibers and terminals b few NPY-IR neurons or fibers. The MPT contains modest numbers of ENK-IR fibers. The APT has no NPY-IR neurons or terminals, but an occasional ENK-IR neuron is seen and there is sparse ENK-IR innervation Peptidergic innervation of the visual nuclei does not appear to be derived from the retina. The results show a set of retinally innervated, contiguous nuclei extending from the thalamic ventrolateral geniculate nucleus dorsomedially to the midbrain CPT. These nuclei plus the superior colliculus comprise a dorsal “visual shell” embracing a central core of caudal thalamus and rostral midbrain.